The broad purpose of this research is to specifically regulate the immune response to one given antigenic molecule, in particular one that serves as a transplantation antigen. These studies will be performed largely with congenic-resistant and recombinant strains of mice that differ from each other only with respect to the H-2D region of the major histocompatibility complex. Our immunosuppressive reagents will be antisera produced against H-2 antigen-specific helper factors. We have already produced a heteroantiserum (rat-anti-mouse) against the supernatants containing antigen-specific factor. The rat antiskin-graft-induced helper factor antisera causes prolongation of skin graft survival. Monoclonal antibodies have been produced from immune rat spleen cells; analysis of their ability to prolong graft survival has not demonstrated immunosuppressive capabilities. Likewise, antisera raised between Ig congenic strains of mice has not led to prolongation of graft survival. We are presently attempting to raise antisera in "double congenic" lines (H-2 and Ig incompatible) and will examine this antisera for immunosuppressive activity. In the event that our initial proposed approach to antigen-specific immunosuppression with specific monoclonal reagents is not satisfactory, we have designed experiments in which we will attempt to induce immunosuppression directly with fractionated H-20 incompatible lymphoid cells. The precise procedure for this latter approach is being determined from studies that we are conducting with "genetic nonresponders" in order to gain a greater understanding of the mechanisms of immunosuppression.